Herpes simplex viral (HSV) infections are caused by two major types of the virus, Type I, which is an oral type and is usually the cause of Herpes labialis, and Type II, which is usually the cause of Herpes genitalis. Both types of virus are common worldwide, and present serious medical and emotional problems to those infected.
HSV infections have been treated with a combination of alpha interferon and the antiviral agent acyclovir (ACV), but cannot be effectively treated with this combination if this treatment is delayed 24 hours after exposure. The combination of interferon and cyclaradine of this invention accomplishes a reduction in virus titer with a low interferon concentration, and is effective even when initiation of treatment is delayed by 24 hours or more after exposure.
The present invention contemplates the combination of cyclaradine with all interferon types, i.e., natural or recombinant alpha (leucocyte), beta (fibroblast) or gamma (immune) interferon, but alpha interferons are preferred. As used herein, the term "alpha interferon" means a natural or recombinant interferon exhibiting biological properties similar to those of human leucocyte interferon. It should be noted that a number of alpha interferon species are known, usually designated by a numeral after the Greek letter, and all are contemplated for use in this invention. Also included within the scope of this invention are the socalled alpha hybrid interferons wherein fragments of two or more native alpha interferon species are joined (See for instance, EP No. 51873). Preferred forms of alpha interferon for use in the formulations of the present invention are alpha-1 and alpha-2 interferon. Particularly preferred for use in the formulations of the present invention is alpha-2 interferon. Alpha-2 interferon may be prepared by recombinant-DNA methods, for example those disclosed by Nagata et al., Nature, Vol. 284, pages 316-320 (1980).
The antiviral agent cyclaradine (i.e. [1R-(1.alpha.,2.beta.,3.beta.,5.beta.)]-3-(6-amino-9H-purin-9-yl)-5-(hydro xymethyl)-1,2-cyclopentanediol) and its preparation are described in U.S. Pat. Nos. 4,383,114, 4,268,672 and 4,138,562. Prodrug alkoxyalkanoate esters (e.g. the 5'-methoxyacetate ester) of cyclaradine are described in U.S. Pat. No. 4,362,729, with the 5'-ethoxypropionate ester and the pharmaceutically acceptable salts thereof being specifically disclosed in a patent application of Robert Vince titled "(3-Ethoxypropionate) Esters of Cyclaradine" filed July 30, 1984. As used herein, "cyclaradine" includes (+)- or (+)- cyclaradine and lower alkoxyalkanoate esters thereof, although (+)-cyclaradine or its esters is preferred.